tbuckley/cabot-search huggingface dataset:
Mechanisms and Consequences of Variable TRPA1 Expression by Airway Epithelial Cells: Effects of <i>TRPV1</i> Genotype and Environmental Agonists on Cellular Responses to Pollutants <i>in Vitro</i> and Asthma
Authors: Emmanuel Rapp, Zhenyu Lu, Lili Sun, Samantha N. Serna, Marysol Almestica-Roberts, Katherine L. Burrell, Nam D. Nguyen, Cassandra E. Deering-Rice, Christopher A. Reilly
Journal: Environmental Health Perspectives (2023)

Background: Transient receptor potential ankyrin-1 [transient receptor potential cation channel subfamily A member 1 (TRPA1)] and vanilloid-1 [transient receptor potential cation channel subfamily V member 1 (TRPV1)] detect inhaled irritants, including air pollutants and have roles in the development and exacerbation of asthma. Objectives: This study tested the hypothesis that increased expression of TRPA1, stemming from expression of the loss-of-function TRPV1 (I585V; rs8065080) polymorphic variant by airway epithelial cells may explain prior observations of worse asthma symptom control among children with the TRPV1 I585I/V genotype, by virtue of sensitizing epithelial cells to particulate materials and other TRPA1 agonists. Methods: TRP agonists, antagonists, small interfering RNA (siRNA), a nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway inhibitor, and kinase activators and inhibitors were used to modulate TRPA1 and TRPV1 expression and function. Treatment of genotyped airway epithelial cells with particulate materials and analysis of asthma control data were used to assess consequences of TRPV1 genotype and variable TRPA1 expression on cellular responses in vitro and asthma symptom control among children as a function of voluntarily reported tobacco smoke exposure. Results: A relationship between higher TRPA1 expression and function and lower TRPV1 expression and function was revealed. Findings of this study pointed to a mechanism whereby NF-κB promoted TRPA1 expression, whereas NF-κB–regulated nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 2 (NLRP2) limited expression. Roles for protein kinase C and p38 mitogen activated protein kinase were also demonstrated. Finally, the TRPV1 I585I/V genotype was associated with increased TRPA1 expression by primary airway epithelial cells and amplified responses to selected air pollution particles in vitro. However, the TRPV1 I585I/V genotype was not associated with worse asthma symptom control among children exposed to tobacco smoke, whereas other TRPA1 and TRPV1 variants were. Discussion: This study provides insights on how airway epithelial cells regulate TRPA1 expression, how TRPV1 genetics can affect TRPA1 expression, and that TRPA1 and TRPV1 polymorphisms differentially affect asthma symptom control. https://doi.org/10.1289/EHP11076
Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain
Authors: Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Martijn Kremer, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Journal: Journal of Hematology & Oncology (2023)

Abstract Background The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. Methods Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones. Results We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN -positive MM cells. TCRs of the most promising T-cell clones were sequenced, cloned into retroviral vectors, and transferred to CD8 T cells. Jchain TCR T cells recognized target cells when JCHAIN and the appropriate HLA restriction alleles were expressed, while JCHAIN or HLA-negative cells, including healthy subsets, were not recognized. Patient-derived JCHAIN -positive MM samples were also lysed by Jchain TCR T cells. In a preclinical in vivo model for established MM, Jchain-A1, -A24, -A3, and -A11 TCR T cells strongly eradicated MM cells, which resulted in 100-fold lower tumor burden in Jchain TCR versus control-treated mice. Conclusions We identified TCRs targeting Jchain-derived peptides presented in four common HLA alleles. All four TCRs demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
Poly‐Catecholic Functionalization of Biomolecules for Rapid Gelation, Robust Injectable Bioadhesion, and Near‐Infrared Responsiveness
Authors: Hossein Montazerian, Alireza Hassani Najafabadi, Elham Davoodi, Rasoul Seyedmahmoud, Reihaneh Haghniaz, Avijit Baidya, Wei Gao, Nasim Annabi, Ali Khademhosseini, Paul S. Weiss
Journal: Advanced Healthcare Materials (2023)

Mussel-inspired catechol-functionalization of degradable natural biomaterials has garnered significant interest as an approach to achieve bioadhesion for sutureless wound closure. However, conjugation capacity in standard coupling reactions, such as carbodiimide chemistry, is limited by low yield and lack of abundant conjugation sites. Here, a simple oxidative polymerization step before conjugation of catechol-carrying molecules (i.e., 3,4-dihydroxy-l-phenylalanine, l-DOPA) as a potential approach to amplify catechol function in bioadhesion of natural gelatin biomaterials is proposed. Solutions of gelatin modified with poly(l-DOPA) moieties (GelDOPA) are characterized by faster physical gelation and increased viscosity, providing better wound control on double-curved tissue surfaces compared to those of l-DOPA-conjugated gelatin. Physical hydrogels treated topically with low concentrations of NaIO
Caloric restriction for the immunometabolic control of human health
Authors: Claudio Procaccini, Paola de Candia, Claudia Russo, Giusy De Rosa, Maria Teresa Lepore, Alessandra Colamatteo, Giuseppe Matarese
Journal: Cardiovascular Research (2023)

Abstract Nutrition affects all physiological processes occurring in our body, including those related to the function of the immune system; indeed, metabolism has been closely associated with the differentiation and activity of both innate and adaptive immune cells. While excessive energy intake and adiposity have been demonstrated to cause systemic inflammation, several clinical and experimental evidence show that calorie restriction (CR), not leading to malnutrition, is able to delay aging and exert potent anti-inflammatory effects in different pathological conditions. This review provides an overview of the ability of different CR-related nutritional strategies to control autoimmune, cardiovascular, and infectious diseases, as tested by preclinical studies and human clinical trials, with a specific focus on the immunological aspects of these interventions. In particular, we recapitulate the state of the art on the cellular and molecular mechanisms pertaining to immune cell metabolic rewiring, regulatory T cell expansion, and gut microbiota composition, which possibly underline the beneficial effects of CR. Although studies are still needed to fully evaluate the feasibility and efficacy of the nutritional intervention in clinical practice, the experimental observations discussed here suggest a relevant role of CR in lowering the inflammatory state in a plethora of different pathologies, thus representing a promising therapeutic strategy for the control of human health.
Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia
Authors: Jianshan Mo, Lin Deng, Keren Peng, Shumin Ouyang, Wen Ding, Linlin Lou, Ziyou Lin, Jianzheng Zhu, Jingwei Li, Qiyi Zhang, Pengyan Wang, Yuanzhen Wen, Xiaobing Chen, Peibin Yue, Jin-Jian Lu, Kai Zhu, Yongjiang Zheng, Yuanxiang Wang, Xiaolei Zhang
Journal: Journal of Hematology & Oncology (2023)

Abstract The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.
Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction
Authors: Emma K. Gard, Anna L. Beale, Fernando Telles, Frank E. Silvestry, Thomas Hanff, Scott L. Hummel, Sheldon E. Litwin, Mark C. Petrie, Sanjiv J. Shah, Barry A. Borlaug, Dan Burkhoff, Jan Komtebedde, David M. Kaye, Shane Nanayakkara
Journal: European Journal of Heart Failure (2023)
Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology
Authors: Finn Gustafsson, Kevin Damman, Sanem Nalbantgil, Linda W. Van Laake, Laurens F. Tops, Thomas Thum, Stamatis Adamopoulos, Michael Bonios, Andrew JS Coats, Maria G. Crespo‐Leiro, Mandeep R. Mehra, Gerasimos Filippatos, Loreena Hill, Marco Metra, Ewa Jankowska, Nicolaas de Jonge, David Kaye, Marco Masetti, John Parissis, Davor Milicic, Petar Seferovic, Giuseppe Rosano, Tuvia Ben Gal
Journal: European Journal of Heart Failure (2023)

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline‐directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end‐of‐life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).
Nrf2 silencing amplifies DNA photooxidative damage to activate the STING pathway for synergistic tumor immunotherapy
Authors: Shengjie Sun, Mian Yu, Liu Yu, Wenxin Huang, Meishu Zhu, Yanan Fu, Lingchen Yan, Qiang Wang, Xiaoyuan Ji, Jing Zhao, Meiying Wu
Journal: Biomaterials (2023)
Human microbiomes in cancer development and therapy
Authors: Chenglai Xia, Jiyan Su, Can Liu, Zhikai Mai, Shuanghong Yin, Chuansheng Yang, Liwu Fu
Journal: MedComm (2023)

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy. We also insight into the molecular mechanisms of triggering, promoting, or inhibiting carcinogenesis and disease progress induced by microbiomes or/and their secretions of bioactive metabolites. And then, the strategies of application of microorganisms in cancer treatment were discussed in detail. However, the mechanisms by which human microbiomes function are still poorly understood. The bidirectional interactions between microbiotas and endocrine systems need to be clarified. Probiotics and prebiotics are believed to benefit human health via a variety of mechanisms, in particular, in tumor inhibition. It is largely unknown how microbial agents cause cancer or how cancer progresses. We expect this review may open new perspectives on possible therapeutic approaches of patients with cancer.
Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation
Authors: Elizabeth Guirado, Cassandra Villani, Adrienn Petho, Yinghua Chen, Mark Maienschein-Cline, Zhengdeng Lei, Nina Los, Anne George
Journal: International Journal of Oral Science (2023)

Abstract X-linked hypophosphatemia (XLH) represents the most common form of familial hypophosphatemia. Although significant advances have been made in the treatment of bone pathology, patients undergoing therapy continue to experience significantly decreased oral health-related quality of life. The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells. Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved. RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation. RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells, while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation. These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.
Prognostic Significance of the Criteria for Metastatic Involvement of Regional Lymph Nodes in Cervical Cancer According to Magnetic Resonance Imaging Findings
Authors: E. G. Zhuk, I. A. Kosenko
Journal: Radiology - Practice (2023)

The objective of this study is to assess the criteria for metastatic involvement of the LN (MLN) according to magnetic resonance imaging (MRI) and to identify the most prognostically significant. The MRI data of 159 removed LN were compared with the results of a morphological study of the resected preparations. ROC- analysis (Receiver Operating Characteristic curve) was used to determine the diagnostic performance of threshold values. The test performance was evaluated depending on the area under the ROC curve — the AUC parameter (Area Under Curve). In order to evaluate the prognostic significance of MRI predictors for metastatic involvement of the LN, uni-and multivariate regression logistic analyses were performed. According to the results of multivariate analysis, the configuration index is less than or equal to 1.65, the absence of a signal from the fatty tissue of the hilum of LN, and perinodular edema are the most prognostically significant criteria for metastatic involvement of the LN (p &lt; 0.05).
Post-traumatic Pseudoaneurysm of Hepatic Artery (Case Report and Literature Review)
Authors: O. A. Vinogradova, A. V. Romanova
Journal: Radiology - Practice (2023)

Pseudoaneurysm (PA) of the hepatic artery is a rare complication of abdominal trauma, iatrogenic injuries (biopsy, endoscopic cholecystectomy, liver transplantation), infections, tumors, vasculitis, acute and chronic pancreatitis. This case report presents a life-threatening complications in a patient who underwent surgery for liver lesion. Due to the use of CT angiography, it was possible to determine the cause of bleeding from the upper gastrointestinal tract, evaluation the localization of pseudoaneurysm and treated with elective management.
Using Intravascular Ultrasound as Experience in a Comorbid Patient of High Surgical Risk
Authors: E. B. Shakhov, E. B. Petrova, A. D. Lyamaev, E. V. Chebotar’, A. A. Shul’ts, S. P. Sharlanov
Journal: Radiology - Practice (2023)

Intravascular ultrasound examination (ICSI) allows to assess the nature of atherosclerotic plaque, the degree of significance and extent of stenosis, as well as to monitor the position of the stent in the lumen of the coronary artery. Insufficient opening of the stent, unrecognized during angiographic control, can lead to thrombosis or restenosis in the early or long term. The clinical case presented in the publication demonstrates the difference between the results of fluoroscopycontrolled stenting and ICSI-controlled stenting during percutaneous coronary intervention (PCI) in a high-risk surgical patient with significant concomitant pathology.
Magnetic Resonance Imaging of Subchondral Insufficiency Fracture of the Medial Femoral Condyle (Clinical Case)
Authors: A. P. Ivankov, P. V. Seliverstov
Journal: Radiology - Practice (2023)

A clinical example is presented that demonstrates the capabilities of magnetic resonance imaging (MRI) in the diagnosis of a subchondral insufficiency fracture of the medial femoral condyle. An MR study protocol has been demonstrated that allows ensure successful diagnosis of this type of fracture.
Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer
Authors: S. Chowdhury, A. Bjartell, N. Agarwal, B.H. Chung, R.W. Given, A.J. Pereira de Santana Gomes, A.S. Merseburger, M. Özgüroğlu, Á. Juárez Soto, H. Uemura, D. Ye, S.D. Brookman-May, A. Londhe, A. Bhaumik, S.D. Mundle, J.S. Larsen, S.A. McCarthy, K.N. Chi
Journal: Annals of Oncology (2023)

The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN.Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model.One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment.Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.
A versatile drug-controlled release polymer brush hybrid non-glutaraldehyde bioprosthetic heart valves with enhanced anti-inflammatory, anticoagulant and anti-calcification properties, and superior mechanical performance
Authors: Tao Yu, Gaocan Li, Xiaotong Chen, Dajun Kuang, Qing Jiang, Yingqiang Guo, Yunbing Wang
Journal: Biomaterials (2023)
Factors associated with receipt of COVID-19 vaccination and SARS-CoV-2 seropositivity among healthcare workers in Albania (February 2021–June 2022): secondary analysis of a prospective cohort study
Authors: Pernille Jorgensen, Alexis Schmid, Jonilda Sulo, Iria Preza, Iris Hasibra, Esther Kissling, Albana Fico, Shela Sridhar, Julia E. Rubin-Smith, Majlinda Kota, Adela Vasili, Rovena Daja, Miljana Nika, Richard Pebody, Kathryn E. Lafond, Mark A. Katz, Silvia Bino
Journal: The Lancet Regional Health - Europe (2023)

Healthcare workers (HCWs) have been disproportionally affected by COVID-19. We investigated factors associated with two- and three-dose COVID-19 vaccine uptake and SARS-CoV-2 seropositivity among 1504 HCWs enrolled (19 February-7 May 2021) in a prospective COVID-19 vaccine effectiveness cohort in Albania through a secondary analysis.We collected sociodemographic, occupational, health, prior SARS-CoV-2 infection, and COVID-19 vaccination data from all HCWs at enrollment. Vaccination status was assessed weekly through June 2022. A serum sample was collected from all participants at enrollment and tested for anti-spike SARS-CoV-2 antibodies. We analyzed HCWs characteristics and outcomes using multivariable logistic regression.By 11 June 2022, 1337 (88.9%) HCWs had received two COVID-19 vaccine doses, of whom 255 (19.1%) received a booster. Factors significantly associated with receiving three doses (adjusted odds ratio (aOR), 95% CIs) were being ≥35 years (35-44 years: 1.76 (1.05-2.97); 45-54 years: 3.11 (1.92-5.05); ≥55 years: 3.38 (2.04-5.59)) and vaccinated against influenza (1.78; 1.20-2.64). Booster dose receipt was lower among females (0.58; 0.41-0.81), previously infected (0.67; 0.48-0.93), nurses and midwives (0.31; 0.22-0.45), and support staff (0.19; 0.11-0.32). Overall 1076 (72%) were SARS-CoV-2 seropositive at enrollment. Nurses and midwifes (1.45; 1.05-2.02), support staff (1.57; 1.03-2.41), and HCWs performing aerosol-generating procedures (AGPs) (1.40; 1.01-1.94) had higher odds of being seropositive, while smokers had reduced odds (0.55; 0.40-0.75).In a large cohort of Albanian HCWs, COVID-19 vaccine booster dose uptake was very low, particularly among younger, female, and non-physician HCWs, despite evidence demonstrating the added benefit of boosters in preventing infection and severe disease. Reasons behind these disparities should be explored to develop targeted strategies in order to promote uptake in this critical population. SARS-CoV-2 seroprevalence was higher among non-physicians and HCWs performing APGs. A better understanding of the factors contributing to these differences is needed to inform interventions that could reduce infections in the future.This study was funded by the Task Force for Global Health (US Centers for Disease Control (CDC) cooperative agreement # NU51IP000873) and the World Health Organization, Regional Office for Europe.
Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms
Authors: Mingqian Fang, Yu Li, Zhiyi Liao, Gan Wang, Qiqi Cao, Ya Li, Yong Duan, Yanbing Han, Xinyi Deng, Feilong Wu, Peter Muiruri Kamau, Qiumin Lu, Ren Lai
Journal: Immunity (2023)